Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion

• Published in: Chinese journal of traumatology Vol. 12; no. 2; pp. 71 - 76
• Main Author: 周君琳 李钢 海涌 关立 黄新莉 孙鹏
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.04.2009; Department of Orthopedics,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China%Peking North Hospital of Ministry of Ordanee Industry of China,Beijing 100089,China%Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,China
• Subjects: Animals; Carbon monoxide; Hindlimb - blood supply; Immunohistochemistry; Intercellular Adhesion Molecule-1 - metabolism; Lung; Lung Injury - etiology; Lung Injury - metabolism; Male; MDA含量; MPO活性; Neutrophils - metabolism; NF-kappa B - metabolism; Nuclear factor kappa B; Organometallic Compounds - pharmacology; Rats; Reperfusion injury; Reperfusion Injury - complications; 一氧化碳; 中性粒细胞; 二甲基亚砜; 急性肺损伤; 细胞间粘附分子-1; 肢体缺血再灌注; Carbon monoxide; Lung; Reperfusion injury; Nuclear factor kappa B; Carbonmonoxide
• ISSN: 1008-1275
• DOI: 10.3760/cma.j.issn.1008-1275.2009.02.002

Objective： To observe the role and mechanism of CO- releasing molecule （CORM）-2 in lung injury induced by ischemia-reperfusion （IR） of hind limbs in rats. Methods： Arat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley （SD） rats were randomly divided into 5 groups （n = 8）： sham, sham ＋ CORM-2, IR, IR ＋ CORM-2 and IR ＋ dimethyl sulfoxide （DMSO）. Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR＋CORM-2 group and in the sham ＋ CORM-2 group were given CORM-2 （10 μmol/kg intravenous bolus） 5 minutes before reperfusion or at the corresponding time points, while rats in the IR ＋ DMSO group was treated with the same dose of vehicle （DMSO） at the same time. The lung tissue structure, polymorphonuclear neutrophil （PMN） count, wet-to-dry weight ratio （W/D）, malondialdehyde （MDA） content, myeloperoxidase （MPO） activity, intercellular adhesion molecule- 1 （ICAM- 1）expression, I κBα degradation and nuclear factor （NF）-κB activity in the lungs were assessed. Results： As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF- κB activity significantly increased in the IR group, but the level of I κBα decresed （P〈0.01）. Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM- 1 expression significantly decreased in the IR＋COMR-2 group （P〈0.01）, while the level of IκBα increased. Conclusions： These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-κB pathway and the leu- kocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.